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APPLICATION OF IMMUNOTHERAPY IN PATIENTS WITH THE DUODENAL ULCER DESEASES Suleymanov S.F. (Republic of Uzbekistan) Email: Suleymanov557@scientifictext.ru
Suleymanov Suleyman Fayzullayevich - PhD in Medicine, Senior Researcher, Head of the Department, DEPARTMENT oF MICROBIOLOGY, VIROLOGY, IMMUNOLOGY AND PHTHISIOLOGY, BUKHARA STATE MEDICAL INSTITUTE, BUKHARA, REPUBLIC OF UZBEKISTAN
Abstract: the article presents data on the study of the immune status of patients with chronic duodenal ulcer deseases (ChDUD). The study of the immune status was conducted in 52 patients with ChDUD and in 36practically healthy individuals. Patients noted suppression by the T-link of immunity and its subpopulations, the voltage of the humoral link of immunity. Conventional treatment methods did not eliminate the immune deficiency in patients with ChDUD. Thymoptinum in a total dose of 1.0 mg - 1.2 mg (per course), used in patients of the 2nd group (n = 24), eliminated immune disorders, increased the whole spectrum of cellular immunity, had an immunocorrective and eradication effect.
Keywords: immune status, chronic duodenal ulcer, thymoptinum, T-system of immunity, humoral immunity, immunotherapy.
ПРИМЕНЕНИЕ ИММУНОТЕРАПИИ У БОЛЬНЫХ С ЯЗВЕННОЙ БОЛЕЗНЬЮ ДВЕНАДЦАТИПЕРСТНОЙ КИШКИ Сулейманов С.Ф. (Республика Узбекистан)
Сулейманов Сулейман Файзуллаевич - кандидат медицинских наук, старший научный сотрудник,
заведующий кафедрой, кафедра микробиологии, вирусологии, иммунологии и фтизиатрии, Бухарский государственный медицинский институт, г. Бухара, Республика Узбекистан
Аннотация: в статье приводятся данные по исследованию иммунного статуса у больных с хронической язвенной болезнью двенадцатиперстной кишки (ХЯБДК). Изучение иммунного статуса было проведено у 52 больных с ХЯБДК и у 36 практически здоровых лиц. У больных отметили супрессию со стороны Т-звена иммунитета и его субпопуляций, напряжение гуморального звена иммунитета. Общепринятые методы лечения не приводили к устранению иммунного дефицита у больных ЯБДК.
Тимоптин в общей дозе 1,0 мг - 1,2 мг (на курс), использованный у больных 2-й группы (n=24), устранял иммунные расстройства, повышал весь спектр клеточного иммунитета, обладал иммунокорригирующим и эрадикационным действием.
Ключевые слова: иммунный статус, хроническая язвенная болезнь двенадцатиперстной кишки, тимоптин, Т-система иммунитета, гуморальный иммунитет, иммунотерапия.
The etiopathogenesis of ChDUD associated with Helicobacter pylori (HP) infection is associated with contamination of the mucous membrane (MM) of the gastroduodenal zone - GDZ (gastric MM - GMM and DMM) with these cytotoxic strains of these bacteria [5]. According to the concept [4], the development of various forms of gastroduodenal pathology depends on the resistance of the microorganism, and HP pathogenic strains can show their cytotoxic effect only when the immunobiological properties of the human body are reduced against the background of the developed immunodeficiency status [2, 3].
The purpose of this study was to study the parameters of immunity in patients with ChDUD and conduct antihelicobacter and immunocorrecting therapy in them.
Materials and methods. 52 patients with ChDUD were examined, of whom 37 (71.2%) were men and 15 (28.8%) women aged from 23 to 54 years. The duration of ulcerative history was on average 6.2 ± 2.4 years. The diagnosis of exacerbation of ChDUD was confirmed endoscopically.
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The average size (diameter) of the ulcers was 0.9 cm. Contamination of the GMM was determined by urease test. All patients showed a high degree of HP infection. Depending on the treatment, the patients were divided into 2 groups: the 1st group (n = 28) received an eradication regimen consisting of Omeprazole (40 mg/day), De-nol (480 mg/day), Tinidazole (1000 mg/day) for 2 weeks; in the 2nd group (n = 24), the same treatment regimen with the 1st group was used, supplemented with Thymoptinum (Uzbekistan) (1 ml of 0.01%) solution subcutaneously every other day; for a course of 10-12 injections).
Cellular immunity was studied using monoclonal antibodies to CD receptors ("Sorbent Ltd", Russia) of the Institute of Immunology of the Ministry of Health and Social Development of the Russian Federation. T-lymphocytes were determined (total population - CD3); T-helpers (subpopulation Th - CD4); T-suppressors (Ts subpopulation - CD8); B lymphocytes (subpopulation of CD19) and immunoregulatory index (IRI) - CD4/CD8. The level of serum immunoglobulins of classes A, M and G was determined according to Mancini (1968). Circulating immune complexes (CIC) were detected by Hascova.
Immunological examination was carried out for 2-5 days after the patient was hospitalized, and also 1 month after the treatment. The control group for comparison of immunological parameters was 36 practically healthy individuals (25-55 years).
Results and discussion. In a retrospective analysis of the results of immunological examination presented in the table, it was found that the acute phase of ChDUD was accompanied by a decrease in the level of the general population of T-lymphocytes (CD3). Differences were found in groups with different outcomes of eradication therapy: patients with the 1st group had a lower T-cell content in the blood than patients with the 2nd group. Also in both groups there was an imbalance of T-cell subpopulations with a decrease in their helper share (CD4) and an increase in the number of suppressors (CD8); a significant decrease in IRI and B-lymphocytes (CD19) was registered, which indicates profound changes in reactivity in patients with ChDUD.
Table 1. Dynamics of changes in the system of immunity status in Patients with ChDUD in the process of
immunomodulatory therapy (M ± m)
Indicators Patients of the 1st group Patients of the 2nd group Control group
CD3(%) A 39 ± 1,2*** 42 ± 1,4*** 43 ± 2,3** 64 ± 2,6*** 51 ± 2
B
CD4(%) A 25 ± 0,9*** 28 ± 1,4*** 23 ± 1,1*** 44 ± 1,6*** 36 ± 0,7
B
CD8 (%) A 15.1 ± 1,4 16.2 ± 1,6 16,5 ± 1,3 19,1 ± 1,0 17 ± 1,2
B
ICI A 1,6 ± 0,2** 1,7 ± 0,1* 1,5 ± 0,2* 2,3 ± 0,2 2,1 ± 0,1
B
CD19(%) A 11 ± 1,2** 13 ± 1,6 11,7 ± 1,5 17,2 ± 2,1 15 ± 1
B
IgA, g/l A 2,2 ± 0,3 2,5 ± 0,5 2,3 ± 0,4 2,9 ± 0,2 2,8 ± 0,3
B
IgM, g/l A 1,3 ± 0,1* 1,02 ± 0,2*** 1,2 ± 0,2* 1,5 ± 0,2 1,6 ± 0,11
B
IgG, g/l A 20,4 ± 0,6*** 19,6 ± 0,7*** 19,4 ± 0,8** 18,7 ± 0,5** 15,9 ± 0,9
B
Note: A - indicators before treatment, B - indicators after treatment; *- p<0.05; **- p<0.01; ***- p<0.001 compared to control.
With exacerbation of ChDUD in both groups, a significant decrease in IgA and IgM levels was observed with a simultaneous increase in IgG indices (p<0.01 in the 1st; p<0.001 in the 2nd group), which indicates violations in the humoral component of the immune system. Changes in immune homeostasis are also accompanied by a significant, 3 -fold increase in the level of the CIC (p<0.001).
The formation of a peptic defect is not only the result of local damage to the DMM against an imbalance of aggression and the protection of HP microbial contamination, but also a consequence of a breakdown in adaptation, an imbalance in the immune system. ChDUD in most patients is associated with intestinal dysbiosis, microbial antigens of which can cause sensitization and exacerbate the immune deficiency in ChDUD patients [1].
Healing of the peptic defect was achieved in a shorter time with successful eradication of HP (in the 1st group - for 24.8 ± 1.2 days with an eradication efficiency of 59%; in the 2nd group - for 17.3 ± 0.46 days with an effectiveness eradication 86%). After treatment, patients with the 1st group had lymphopenia; the level of the total population of T-lymphocytes CD3 (Table) was reduced, as was its helper CD4 fraction (p<0.01) with a high level of CD8 suppressors, which was significantly different from the corresponding parameters of the 2nd group. A reduction in the IRI to 1.5 at a rate of 2.1 confirms the imbalance in the CD4/CD8 system in patients with ineffective eradication.
Patients of the 2nd group, after immunocorrective therapy, showed an effective increase in the number of T (CD3), B cells (CD19) (Table), with a simultaneous increase in the proportion of Th (CD4) and IRI to 2.3 (normal 2.1), which was much higher than similar values from the 1st group (p<0.001). Apparently, a positive shift in the functioning of the T-cell (an increase in CD3, CD4 and a decrease in CD8) component of the immune system contributes to the eradication of HP. In addition, an increase in B-lymphocytes (CD19) and IgA levels was observed in this group compared to the data before treatment (p<0.001).
Thus, ChDUD in the recurrence stage is characterized by a deep deficit of most of the parameters of the body's immune system with a high HP infection of GMM and DMM. Predictors of ineffective eradication are a significant decrease in the number of CD3, CD4 and IRI, as well as a decrease in the concentration of IgA. On the contrary, clinical and endoscopic remission of patients of the 2nd group (immunomodulating therapy) was accompanied by a significant increase in the parameters of cellular-humoral immunity, which positively affected the results of eradication and immunocorrective therapy.
References / Список литературы
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